This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Electrical activities of living cells are coupled to the fast long-distance information flow in the nervous system and are subject of great scientific and medical interests. Nevertheless, the existing observation methods for electrical activity have various limitations. We proposed that membrane electromotility (MEM), which arise from the intrinsic property of cell membrane, can be used as an optical indicator of cell electrical activity. Since it relies on an endogenous mechanism, this approach is free of bleaching and toxicity. Also the sample preparation will be simpler. But optical detection of MEM signals poses a significant challenge due to its extremely small size (~nm). We achieved this sub-nanometer sensitivity by combining low-coherence diffraction phase microscope (LCDPM) with frequency domain detection. We demonstrated that our technique performs non-invasive, dye-less optical imaging of cell electrical activities from electrically stimulated human cell lines. We are working on to improve the instrument and analysis method so that MEM signals can be detected in reflection mode which has a greater potential for medical applications.